The goal of this project is to develop methodology to prime cytotoxic T lymphocyte (CTL) immunity to Human Immunodeficiency Virus and other pathogens using nonliving vaccines. Currently, optimal methods do not exist to prime this critical form of immunity to viruses. The development of efficacious vaccines to these pathogens would be of great benefit to both man and animals. Two novel approaches are being taken. The first approach will prime CTL's with peptides by exploiting the observation that peptides associate with class I Major Histocompatibility Complex (MHC) molecules upon reassociation of beta2-microglobulin. Methods will be developed for introducing peptides and beta2-microglobulin in-vivo in a manner that will form peptide-class I MHC molecule complexes and prime CTL's. The second approach will prime CTL's with intact proteins by exploiting the observation that native antigens can be presented to CTL's by a specialized antigen-presenting cell resident in normal tissues. We will develop suitable methods for enhancing antigen entry into this pathway of antigen-presentation. These approaches will be developed for vaccines in association with murine, and then human class I MHC molecules.